Disorders of Muscle

Question 1

Duchenne Muscular Dystrophy

Answer 1

X-linked recessive deletion of dystrophin gene.

Early onset (around2, before 5) of proximal weakness with pseudohypertrophy of esp. the calves.

Cardiomyopathies, respiratory failure, cognitive impairment

Question 2

Becker Muscular Dystrophy

Answer 2

X-linked recessive out of frame mutation for dystrophin.

Later age of onset (5-15) with less severe disease–usually no cardiomyopathy.

Question 3

Limb Girdle Muscular Dystrophy

Answer 3

Usually autosomal recessive, sarcoglycan mutation.

Shoulder and pelvic girdle muscle involvement.

Late childhood/early adolescent onset.

Question 4

Fascioscapulohumeral Muscular Dystrophy

Answer 4

Autosomal dominant mutation of DUX8 gene on chromosome 4q.

Onset during adolescence with hallmark facial weakness, along with neck/shoulder/peroneal involvement.

Prominent scapular “winging.”

Question 5

Emery-Dreifuss Muscular Dystrophy

Answer 5

XLR, AD, AR mutations

Childhood onset with slow progression.

Contractures/weakness/wasting with cardiac involvement.

Question 6

DM1 (myotonic muscular dystrophy 1)

Answer 6

CTG repeat on DMPK gene, chromosome 19

Distal muscle involvement with frontal balding, cataracts, cardiac involvement, respiratory insufficiency, and intellectual impairment.

Question 7

DM2 (myotonic muscular dystrophy 2)

Answer 7

CCTG repeat on ZNF9, chromosome 3

Proximal muscle involvement, cataracts

Question 8

Myotonia Congenita

Answer 8

CLCN1 gene with generalized myotonia WITHOUT weakness–stiffness exacerbated by cold/inactivity and relieved by exercise.
AD form - Thomsen Disease
AR form - Becker Disease

Question 9

Central Core Disease

Answer 9

Congenital myopathy that may be associated with malignant hyperthermia as complication of general anesthesia (RYR1 mutation).

On bx, would see clear central “core.”

Question 10

Glycogen Storage Diseases

Type II, III, V, VII

Answer 10

Type II (Pompe Disease): acid maltase (alpha glucosidase) deficiency with muscle weakness and respiratory difficulty.

Type III (Cori Disease): glycogen debranching enzyme deficiency with myopathy

Type V (McArdle Disease): myophophorylase deficiency with exercise intolerance, rhabdomyolysis

Type VII ( Tarui Disease): PFK deficiency with exercise intolerance, muscle cramping

Question 11

Lipid Storage Diseases

Answer 11

Childhood onset - more severe with myopathy, cardiomyopathy, hepatomegaly, and encephalopathy
Adult onset - less severe with fatigability, muscle pain, myoglobinuria

Question 12

Mitochondrial Myopathies

Kearns-Sayre Syndrome
MERRF
MELAS
MNGIE

Answer 12

Clinically heterogeneous group of disorders caused by defective oxidative phosphorylation through MATERNAL inheritance pattern.

Biopsy with Gomori stain reveals “ragged red fibers,” which are accumulations of abnormal mitochondria.

Kearns-Sayre syndrome: progressive external ophthalmoplegia, pigmentary degeneration of retina, cardiomyopathy

MERRF: myoclonic epilepsy with ragged red fibers

MELAS: mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes

MNGIE: mitochondrial neurogastrointestinal encephalopathy syndrome due to thymidine phosphorylase mutation

Question 13

Dermatomyositis

Answer 13

Microangiopathy of the skin and muscle with muscle ischemia due to complement deposition

CD4 mediated inflammatory infiltration

Proximal > distal, legs > arms

Gottron’s papules, malar rash, heliotrope rash

Question 14

Polymyositis

Answer 14

Symmetric proximal weakness with bulbar symptoms and no skin involvement

CD8 mediated infiltration with muscle necrosis on bx

Question 15

Inclusion Body Myositis

Answer 15

Most common myopathy in patients > 50, men > women

Early, often asymmetric weakness of quads, finger flexors, ankle dorsiflexors

Dysphagia and facial weakness

Rimmed vacuoles in biopsy.

DOES NOT RESPOND TO IMMUNOMODULATING THERAPY/STEROIDS.